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Purpose A Benchmark Case (BC) was performed as part of the quality assurance process of the randomized phase 2 GORTEC 2014-14 OMET study, testing the possibility of multisite stereotactic radiation therapy (SBRT) alone in oligometastatic head and neck squamous cell carcinoma (HNSCC) as an alternative to systemic treatment and SBRT. Material and methods Compliance of the investigating centers with the prescription, delineation, planning and evaluation recommendations available in the research protocol was assessed. In addition, classical dosimetric analysis was supplemented by quantitative geometric analysis using conformation indices. Results Twenty centers participated in the BC analysis. Among them, four major deviations (MaD) were reported in two centers. Two (10%) centers in MaD had omitted the satellite tumor nodule and secondarily validated after revision. Their respective DICE indexes were 0.37 and 0 and use of extracranial SBRT devices suboptimal There were significant residual heterogeneities between participating centers, including those with a similar SBRT equipment, with impact of plan quality using standard indicators and geometric indices. Conclusion A priori QA using a BC conditioning the participation of the clinical investigation centers showed deviations from good SBRT practice and led to the exclusion of one out of the twenty participating centers. The majority of centers have demonstrated rigorous compliance with the research protocol. The use of quality indexes adds a complementary approach to improve assessment of plan quality.

International audience; Nasopharyngeal cancers are a rarity in France. Radiotherapy is the cornerstone of treatment, frequently combined with chemotherapy. The technical modality of radiotherapy is complex in this disease, which is located in the vicinity of numerous organs at risk. In this article, we will present the updated guidelines of the French society for radiation oncology (Société française de radiothérapie oncologique, SFRO) on the indications, and technical details of radiotherapy in nasopharyngeal cancers.

Adjuvant radiotherapy is an essential component of the treatment of breast cancer. After conservative surgery for an infiltrating carcinoma, radiotherapy must be systematically performed, regardless of the characteristics of the disease, because it decreases the rate of local recurrence and by this way, specific mortality. A boost dose over the tumour bed is required if the patient is younger than 50 years-old. Partial breast irradiation could be routinely proposed as an alternative to whole breast irradiation, but only in selected and informed patients. For ductal carcinoma in situ, adjuvant radiotherapy must be also systematically performed after lumpectomy. After mastectomy, chest wall irradiation is required for pT3-T4 tumours and if there is an axillary nodal involvement, whatever the number of involved lymph nodes. After neoadjuvant chemotherapy and mastectomy, in case of pN0 disease, chest wall irradiation is recommended if there is a clinically or radiologically T3-T4 or node positive disease before chemotherapy. Axillary irradiation is recommended only if there is no axillary surgical dissection and a positive sentinel lymph node. Supra- and infraclavicular irradiation is advised in case of positive axillary nodes. Internal mammary irradiation must be discussed case by case, according to the benefit/risk ratio (cardiac toxicity). Hypofractionation regimens (42.5Gy in 16 fractions, or 41,6Gy en 13 or 40Gy en 15) are equivalent to conventional irradiation and must prescribe after tumorectomy in selected patients. Delineation of the breast, the chest wall and the nodal areas are based on clinical and radiological evaluations. 3D-conformal irradiation is the recommended technique, intensity-modulated radiotherapy must be proposed only in specific clinical situations. Respiratory gating could be useful to decrease the cardiac dose. Concomitant administration of chemotherapy in unadvised, but hormonal treatment could be start with or after radiotherapy.

Purpose Endoscopic endonasal surgery (EES) is becoming a standard for most malignant sinonasal tumours. Margin analysis after piecemeal resection is complex and optimally relies on accurate histosurgical mapping. Postoperative radiotherapy may be adapted based on margin assessment mapping to reduce the dose to some sinonasal subvolumes. We assessed the use of histosurgical mapping by radiation oncologists (RO). Material and methods A French practice survey was performed across 29 ENT expert RO (2 did not answer) regarding integration of information on EES, as well as quality of operative and pathology reportsto refine radiotherapy planning after EES. This was assessed through an electronic questionnaire. Results EES was ubiquitously performed in France. Operative and pathology reports yielded accurate description of EES samples according to 66.7% of interviewed RO. Accuracy of margin assessment was however insufficient according to more than 40.0% of RO. Additional margins/biopsies of the operative bed were available in 55.2% (16/29) of the centres. In the absence of additional margins, quality of resection after EES was considered as microscopically incomplete in 48.3% or dubious in 48.3% of RO. As performed, histosurgical mapping allowed radiotherapy dose and volumes adaptation according to 26.3% of RO only. Conclusions Standardized histosurgical mapping with margin and additional margin analysis could be more systematic. Advantages of accurate EES reporting could be dose painting radiotherapy to further decrease morbidity in sinonasal tumours.

It is proposed to delineate the anatomo-clinical target volumes of primary tumor (CTV-P) in ethmoid cancers treated with post-operative radiotherapy. This concept is based on the use of radioanatomy and the natural history of cancer. It is supported by the repositioning of the planning scanner with preoperative imaging for the replacement of the initial GTV and the creation of margins around it extended to the microscopic risk zones according to the anatomical concept. This article does not discuss the indications of external radiotherapy but specifies the volumes to be delineated if radiotherapy is considered.

Advances in the reconstructive surgery and minimally invasive endonasal endoscopic surgery of head and neck is poorly evaluated in terms of their impact on radiotherapy planning and outcomes. These surgical advances have resulted in reduced morbidity with equivalent or better tumor control. In the absence of a recommendation on how to delineate target volumes in patients with flaps or to consider margins after endoscopic endonasal surgery, radiotherapy practices are inevitably heterogeneous. Efforts are needed to increase the therapeutic index of postoperative radiotherapy in these situations. We analysed the rare existing literature and outlined a preliminary basis for a recommendation. Strengthening of multidisciplinarity to accurately define target volumes in these complex and relatively new situations, and "delineation concertation meetings" between radiologists, surgeons and radiation oncologists could probably contribute to improved outcomes.

International audience; Concurrent chemoradiotherapy improves the outcome of locally advanced head and neck cancers and the current reference chemotherapy is cisplatin. These results are obtained at the cost of increased toxicities. To limit the risk of toxicity, organ at riskdose constraints have been established starting with 2D radiotherapy, then 3D radiotherapy and intensity-modulated radiotherapy. Regarding grade ≥3 acute toxicities, the scientific literature attests that concurrent chemoradiotherapy significantly increases risks of mucositis and dysphagia. Constraints applied to the oral mucosa volume excluding the planning target volume, the pharyngeal constrictor muscles and the larynx limit this adverse impact. Regarding late toxicity, concurrent chemoradiotherapy increases significantly the risk of postoperative neck fibrosis and hearing loss. However, for some organs at risk, concurrent chemotherapy appears to increase late radiation induced effect, even though the results are less marked (brachial plexus, mandible, pharyngeal constrictor muscles, parotid gland). This additional adverse impact of concomitant chemotherapy may be notable only when organs at risk receive less than their usual dose thresholds and this would be vanished when those thresholds are exceeded as seems to be the situation for the parotid glands. Until the availability of more robust data, it seems appropriate to apply the principle of delivering dose to organs at risk as low as reasonably achievable.

Advances in the reconstructive surgery and minimally invasive endonasal endoscopic surgery of head and neck is poorly evaluated in terms of their impact on radiotherapy planning and outcomes. These surgical advances have resulted in reduced morbidity with equivalent or better tumor control. In the absence of a recommendation on how to delineate target volumes in patients with flaps or to consider margins after endoscopic endonasal surgery, radiotherapy practices are inevitably heterogeneous. Efforts are needed to increase the therapeutic index of postoperative radiotherapy in these situations. We analysed the rare existing literature and outlined a preliminary basis for a recommendation. Strengthening of multidisciplinarity to accurately define target volumes in these complex and relatively new situations, and "delineation concertation meetings" between radiologists, surgeons and radiation oncologists could probably contribute to improved outcomes.

It is proposed to delineate the anatomo-clinical target volumes of primary tumor (CTV-P) in ethmoid cancers treated with post-operative radiotherapy. This concept is based on the use of radioanatomy and the natural history of cancer. It is supported by the repositioning of the planning scanner with preoperative imaging for the replacement of the initial GTV and the creation of margins around it extended to the microscopic risk zones according to the anatomical concept. This article does not discuss the indications of external radiotherapy but specifies the volumes to be delineated if radiotherapy is considered.

Post-therapeutic follow-up of patients with head and neck cancer involves numerous professionals. The radiation oncologist should play an active role in this process. His oncological knowledge and technical expertise position him as a cornerstone for the detection of recurrences from the treated tumor, the research of second primary cancers and the screening of potential side-effects induced by the different treatments administered. To improve the benefits/costs ratio and allow good patient-compliance, follow-up programs should be built through close collaboration between the different contributors and planned according to a feasible schedule. Paraclinical exams must be arranged to respond to accurate objectives. Patient-education is essential to ensure the patient's full understanding and active participation. Finally, the transfer of the long-term follow-up of cancer survivors from specialists to primary care physicians is relevant but would require a prospective evaluation of its efficiency for this specific population.

Highlights • The delineation of target volumes for Head and Neck IMRT is complex. • There have been several approaches for the delineation of the primary tumor clinical target volume: the anatomical guidelines, the geometric guidelines and more recently the international guidelines., Purpose Three methods have been recently proposed for the delineation of the primary tumor clinical target volume (CTV-P) in Head and Neck Cancers: the anatomic method popularized in the French literature by Lapeyre et al. the geometric methods proposed by the DAHANCA group, and more recently the international guidelines promoted by Grégoire et al. integrating the latter two. The aim of this study was to perform a volumetric and dosimetric comparison of the French and the International consensus methods in laryngeal SCC. Patients and methods Two radiation oncologists independently delineated the high dose and low dose primary tumor CTV in four patients with T2 or T3 N0-M0 laryngeal SCC following either the so-called French guidelines or the International guidelines. For the 4 cases, the GTV was delineated by a single radiation oncologist. Nodal CTVs were delineated by one radiation oncologist for the 4 cases using International guidelines. Dose optimization was then performed with VMAT (MONACO version 5.11) using 6 MeV photons. Differences in target volumes and dose distributions in OARs and PTVs were then evaluated with various metrics such as the DICE Similarity Coefficient and the homogeneity index. Results Major differences were observed in the CTV delineation between the 2 delineation methods for the low dose volumes and to a lower extend for the high dose volumes. These differences translated into variations in dose distribution favoring the International guidelines for decreasing dose to various OARs. Such differences toned down when dose distribution on the primary tumors PTVs and nodal PTVs were combined. Conclusion This study demonstrated large differences in CTV delineation between the 2 delineation guidelines. Such differences translated into differences in dose distribution.

Intensity modulated radiation therapy (IMRT) and brachytherapy are standard techniques for the irradiation of oral cavity cancers. These techniques are detailed in terms of indication, preparation, delineation and selection of the volumes, dosimetry and patient positioning control.

The addition of everolimus to exemestane is recommended in patients with HR+ advanced breast cancer with disease recurrence or progression following prior non-steroidal aromatase inhibitors. We report a case of radiation recall syndrome in a breast cancer patient, after introduction of everolimus. A woman with a right breast cancer underwent a mastectomy, then adjuvant chemotherapy, radiation therapy and hormonotherapy. In a phase III trial (UNIRAD protocol), she received everolimus 5 months after radiation therapy. Seven days after introduction, she was suffering from a radiation recall syndrome with exacerbation skin reactions. The exact pathophysiological mechanism of radiation recall syndrome is unknown. The combination of radiation therapy and mTor inhibitor, even sequentially, should be done with caution as several cases have already been reported.

The GORTEC 2017-03-Stereo-postop study is a phase 2, multicentric, nationwide study, funded by the hospital clinical research program (PHRC). The sponsor is Centre Jean-Perrin in Clermont-Ferrand, in partnership with the GORTEC. The principal investigators are Dr J Biau and Dr M Lapeyre. The main objective is to study severe late toxicity of postoperative stereotactic radiotherapy (6×6Gy) for early stage oropharyngeal and oral cavity cancer with high risk margins. The secondary objectives include acute toxicity, efficacy, nutritional impact and quality of life. The population is adult patients, with pT1 or pT2 squamous cell carcinoma of the oropharynx or oral cavity (except lips), without indication of neck irradiation or concomitant chemotherapy, with at risk margin (R1, less than 5mm or uncertain). Ninety patients will be included over a 2-year period; this was calculated to limit the rate of 2-year severe toxicity at 5 to 15%, with a 2-year local control of at least 80 to 90%. If this study is considered as positive, stereotactic radiotherapy (6×6Gy) could become the third therapeutic option, with brachytherapy and normofractionated intensity-modulated radiotherapy (IMRT), for postoperative irradiation of oropharyngeal and oral cavity cancer with high risk margins.

Objectif de l’etude La structuration et la standardisation des donnees medicales a large echelle est un enjeu actuel majeur pour l’optimisation des soins. Materiel et methode Nous developpons un modele multicentrique synchronise base sur le logiciel OIS MOSAIQ® en collaboration avec Elekta. Trois objectifs ont ete definis : la saisie de donnees cliniques de vie reelle structurees dans le dossier medical, la creation automatique de courriers et la creation d’un outil de restitution des donnees. Trois types de formulaires de consultation ont ete crees : initiale, en cours et apres l’irradiation, avec une sous-segmentation anatomique (tete, cou, sein, etc.). Resultats Vingt et un formulaires regroupant 228 champs structures (selon la Common Terminology Criteria for Adverse Events, eCRF [electronic Case Report Form], date de recidive, etc.) ont ete crees avec une ergonomie permettant une saisie rapide. Leurs contenus ont ete definis par 16 medecins de quatre etablissements. La production automatique de document permet un resultat clair en format courrier avec un gain de temps medical. Le logiciel restitue dans une table les donnees des formulaires, les donnees tumorales (TNM, CIM-10 [Classification internationale des maladies, 10e revision], etc.), les irradiations (dose, etalement, etc.). De janvier 2016 a decembre 2017, au centre Paul-Strauss, 318 889 donnees ont ete collectees par l’equipe de radiotherapie, avec une moyenne mensuelle de 15 182. Soixante pour cent des oncologues radiotherapeutes utilisaient les formulaires. De multiples evaluations prospectives ont ete realisees (taux de dermite par medecin, par technique, mucite, etc.), avec la possibilite d’emettre des alertes automatiques de detection precoce de toxicite. Ce modele a aussi ete synchronise sur Mosaiq® a l’institut Jean-Godinot depuis avril 2018. Une large diffusion multicentrique est prevue. Conclusion Cette capture massive de donnees, integree dans la pratique clinique, permet un large panel d’exploitations en cours de developpement comme la modelisation de l’irradiation (controle tumoral et toxicite) et la creation d’alertes. Ce modele est implementable dans les OIS Mosaiq® et certains systemes d’information hospitaliers de facon multicentrique.

Intensity modulated radiation therapy (IMRT) and brachytherapy are standard techniques for the irradiation of oral cavity cancers. These techniques are detailed in terms of indication, preparation, delineation and selection of the volumes, dosimetry and patient positioning control.

Given the ballistic opportunities it offers, intensity-modulated radiotherapy has emerged as the gold standard treatment for head and neck cancers. Protection of organs at risk is one of the objectives of optimization during the planning process. The compliance of dose constraints to the nervous system must be prioritized over all others. To avoid complications, it is recommended to respect a maximum dose of 50Gy to the spinal cord, and 60Gy to the brachial plexus using conventional fractionation of 2Gy per fraction. These constraints can be adapted depending on the clinical situation; they will probably be refocused by the follow-up of the IMRT studies.

Modern techniques such as intensity modulated radiation therapy (IMRT) have been proven to significantly decrease the dose delivered to the cochleovestibular apparatus, limiting consecutive toxicity especially for sensorineural hearing loss. However, recent data still report a 42% rate of radio-induced hypoacusia underscoring the need to protect the cochleovestibular apparatus. Due to the small size of the cochlea, a precise dose-volume analysis could not be performed, and recommendations only refer to the mean dose. Confusing factors such as age, concomitant chemotherapy, primary site and tumor stage should be taken into account at the time of treatment planning. (Non-coplanar) VMAT and tomotherapy have been proven better at sparing the cochlea in comparison with 3D CRT. Brainstem radio-induced injuries were poorly studied because of their infrequency and the difficulty of distinguishing between necrosis and tumor progression in the case of a primary tumor located at the base of skull. The following toxicities have been described: brainstem focal radionecrosis, cognitive disorders without dementia, cranial nerve injuries and sensori motor disability. Maximal dose to the brainstem should be kept to 54Gy for conventional fractionation. This dose could be exceeded (no more than 10mL should receive more than 59Gy), provided this hot spot is located in the peripheral area of the organ.

Intensity-modulated radiation therapy (IMRT) is the gold standard for head and neck irradiation. It allows better protection to the organs at risk such as salivary glands and mandible, and can reduce the frequency of xerostomia, trismus and osteoradionecrosis. At the time of treatment planning, the mean dose to a single parotid gland should be kept below 26Gy, the mean dose to a single submandibular gland below 39Gy, the mean dose to the mandible below 60 to 65Gy and the D2% to a single temporomandibular joint below 65Gy. These dose constraints could be further improved with data extracted from cohorts of patients receiving IMRT exclusively. The dose administered to the target volumes should not be lessened to spare the salivary glands or mandible.

Radiation-induced damage of ocular, orbital and eyelid structures are mainly reported for the optic nerve, retina, lens and lacrimal gland. Dose-volume relationships are, however, inaccurate due to the small volume of most of the organs at risk involved and limited ability of irradiation techniques to spare these structures in the pre-IMRT (intensity-modulated radiation therapy) era. The ability of newest radiation techniques including IMRT and proton therapy to generate steep dose gradients may yield more accurate models in the future. Some toxicities are severe and irreversible, leading to vision loss, as in the case of radiation-induced optic neuropathy for which curative treatments are suboptimal. Other toxicities can lead to reversible vision loss but can be surgically corrected, as is the case for radiation-induced cataract. In this paper, we will review the dose effects for the ocular; orbital and eyelid structures.

Radio-induced pharyngolaryngeal chronic disorders may challenge the quality of life of head and neck cancer long survivors. Many anatomic structures have been identified as potentially impaired by irradiation and responsible for laryngeal edema, dysphonia and dysphagia. Some dose constraints might be plausible such as keeping the mean dose to the pharyngeal constrictor muscles under 50 to 55Gy, the mean dose to the supra-glottic larynx under 40 to 45Gy and, if feasible, the mean dose to the glottic larynx under 20Gy. A reduction of the dose delivered to the muscles of the floor of the mouth and the cervical esophagus would be beneficial as well. Nevertheless, the publications available do not provide an extensive enough level of proof. One should consider limiting as low as possible the dose delivered to these structures without compromising the quality of irradiation of the target tumor volumes.

Objectif de l’etude Des taux heterogenes de recidive locale sont observes chez des patientes atteintes de cancers du sein avec des facteurs pronostiques similaires. Une des hypotheses expliquant ces recidives locales est que certains cancers sont initialement radioresistants. L’objectif de cette etude etait d’identifier des biomarqueurs genetiques de radioresistance du cancer du sein. Materiel et methode Le profil genetique tumoral de 162 patientes inclus dans l’essai ProfiLER (NCT01774409) entre 2013 et 2016 a ete determine par sequencage haut debit et puce d’hybridation genomique comparative. L’association entre les alterations genetiques (mutations, amplifications, deletions) et les caracteristiques des patients a ete analysee. Seules les alterations genetiques presentes dans plus de 3 % des tumeurs ont ete prises en compte. Tous les patients avaient beneficie d’une radiotherapie locale. Resultats Un total de 218 alterations genetiques a ete mis en evidence, dont 18 retrouvees dans plus de 3 % des tumeurs. Une seule alteration genetique etait correlee statistiquement avec le risque de recidive locale. Les patientes atteintes d’une tumeur avec une mutation de PIK3CA (n = 34, 21 %) avaient une duree mediane de survie sans progression locale de 19,8 ans, contre 9,1 ans pour les patientes atteintes de tumeur sans mutation (hazard ratio [HR] : 0,29 ; intervalle de confiance a 95 % [IC95 %] : 0,13–0,64 ; p = 0,002 en analyse unifactorielle). La mutation de PIK3CA a ete identifiee comme etant un facteur protecteur independant de recidive locale en analyse multifactorielle (HR : 0,27 ; IC95 % : 0,09–0,82 ; p = 0,02). Par ailleurs, les patientes atteintes d’une tumeur avec une mutation de ROS1 (n = 8, 4,9 %) avaient une duree mediane de survie sans progression locale de 4 ans, contre 16,1 ans pour les patients atteintes de tumeur non mutee (HR : 2,5 ; IC95 % : 1,74–7,05 ; p = 0,08). Conclusion La mutation de PIK3CA etait associee avec un risque plus faible de recidive locale, dans cette population de patients traites pour des cancers du sein. Ces resultats sont en accord avec des donnees precliniques recentes suggerant que PIK3CA a un impact sur la radiosensibilite.

Radiochemotherapy without surgical resection has become the treatment of choice for anal squamous-cell carcinoma. The optimal treatment for rectal squamous-cell carcinoma is not well established.The purpose of this work was to assess the efficacy of nonoperative strategies in the management of primary rectal squamous-cell carcinoma.We retrospectively reviewed data from all of the patients with documented rectal squamous-cell carcinoma who were treated with conservative strategies in a single institution. Concomitant radiochemotherapy was proposed to all except 1 patient. The remaining patient was treated by radiotherapy alone given his impaired functional status. All of the patients were treated with conformal or intensity-modulated radiation therapy. Surgical resection was reserved for persistent disease or relapse.This study was conducted in a single tertiary institution.After a mean follow-up of 56 months, 2 patients experienced relapse and no patients died.Eleven patients were included in the series. The clinical response to radiotherapy was complete for 7 patients. The remaining 4 patients underwent salvage surgery. The pathologic response was incomplete for 2 of the 4 patients. One recurrence occurred outside the field of radiotherapy and was successfully treated by radiotherapy. The second was a local recurrence, which occurred on a patient who was treated with radiotherapy alone.The number of patients included in this retrospective series was limited because of the rarity of the disease. Patients were treated with nonhomogeneous conservative strategies because of modification in the therapeutic strategy for anal squamous-cell carcinoma and of the adaptation of the treatment to patient comorbidities and functional status.This series demonstrates that good results can be obtained by using a rectum-conserving strategy. Close follow-up should be maintained, with the use of salvage surgery reserved only for persistent disease or relapse (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A155).

Resume Objectif de l'etude. – Realiser une evaluation prospective de la radiotherapie conformationnelle avec modulation d'intensite (RCMI) pour les carcinomes epidermoides des voies aerodigestives superieures avec irradiation bilaterale du cou. Patients et methodes. – De janvier 2002 a aout 2003 au centre Alexis Vautrin, 23 patients ont ete traites par irradiation conformationnelle avec modulation d'intensite pour un cancer des voies aerodigestives superieures. Les dix premiers patients avec un recul de plus de trois mois ont ete analyses. Il s'agissait de cancers de l'oropharynx avec quatre femmes pour six hommes. L'âge moyen etait de 50 ans (39–66). Il y avait huit cancers de stades I –II et deux de stades III-IV. Le CTV1 (volumes cibles anatomocliniques) correspondait a la maladie microscopique (dose prescrite : 50 Gy) et le CTV2 a la maladie macroscopique et a risque (dose prescrite : 66–70 Gy). Les volumes cibles previsionnels (PTV) incluaient au volumes cibles anatomocliniques plus une marge de 5 mm. La RCMI a ete realisee en mode dynamique. Les contentions etaient de type cinq points thermoformees. Les controles de repositionnement ont ete faits par recalage des images portales. Cinq patients (groupe A) ont eu une RCMI de 50 Gy (2 postoperatoires et 3 suivies d'un boost de curietherapie de dose moyenne de 27,5 Gy), et cinq patients (groupe B) une RCMI de 66–70 Gy (4 postoperatoires). La toxicite aigue et tardive a ete cotee selon la classification du Radiation Therapy Oncology Group et de l'European Organization for Research and Treatment of Cancer. Resultats. – Le recul moyen etait de 7,4 mois (3–18,5). Les deplacements etaient de moins de 4 mm dans 98 % des cas. Il n'y a eu aucune recidive locoregionale et aucun deces. Les CTV2 et CTV1 etaient couverts a 100 % par l'isodose 95 % de la dose prescrite. Pour la parotide controlaterale, en moyenne, la dose moyenne etait de 25,5 Gy dans le groupe A contre 31 Gy dans le groupe B (p = 0,09). La dose moyenne de moins de 26 Gy a ete respectee dans 3/5 cas du groupe A contre 0/5 du groupe B (p = 0,04). La toxicite aigue cutanee etait de grade 1 dans cinq cas, grade 2 dans quatre cas et de grade 3 dans un cas. La toxicite aigue muqueuse etait de grade 1 dans trois cas, grade 2 dans cinq cas et de grade 3 dans deux cas. A trois mois, il a ete observe une xerostomie tardive de grades 0–1 dans 50 % des cas. Conclusions. – Les contraintes de dose de moins de 26 Gy a la parotide controlaterale sont plus faciles a satisfaire pour des doses maximum prescrites de 50 Gy. La toxicite aigue a ete faible. L'expansion du volume cible anatomoclinique au volume cible previsionnel peut etre reduite a 4 mm, ce qui devrait ameliorer la dose moyenne aux parotides. A trois mois, le taux de 50 % de xerostomie de grades 0–1 laisse esperer un tres faible taux a deux ans.

Objectif de l’etude Dans 3 a 5 % des cas, l’exophtalmie de Basedow est caracterisee par une atteinte inflammatoire severe pouvant entrainer des sequelles orbitaires. La corticotherapie intraveineuse est parfois inefficace, l’objectif de cette etude etait de montrer l’interet de l’irradiation orbitaire. Materiel et methode L’analyse retrospective a porte sur les dossiers de20 patients traites de 2011 a 2016 principalement dans le centre Leon-Berard. Tous les patients souffraient d’une exophtalmie severe definie par un score clinique d’activite superieur ou egal a 3, etabli en consultation specialisee dans l’exophtalmie de Basedow de l’hopital Wertheimer. Quatorze patients ont beneficie d’une corticotherapie intraveineuse selon un protocole standard (500 mg hebdomadaires sur six semaines puis 250 mg hebdomadaires sur six semaines). La radiotherapie a delivre une dose totale de 20 Gy en dix seances de 2 Gy par deux faisceaux lateraux droit et gauche 6 MV dans un volume retro-orbitaire. Trois patients ont ete irradies dans un seul œil devant une atteinte unilaterale avec modulation d’intensite. Resultats L’efficacite etait definie par un score clinique d’activite strictement inferieur a 2 ou par une diminution d’au moins deux points. Tous les patients ont ete revus pour leur premiere consultation apres l’irradiation entre 3 semaines et 7 mois avec un bilan ophtalmologique, 80 % des patients ont beneficie d’une reponse complete au traitement. Six patients (30 %) ont souffert d’une toxicite aigue de grade 1-2 (principalement des conjonctivites, dans cinq cas sur six). Aucune toxicite de grade 3-4 n’a ete observee. Conclusion La radiotherapie orbitaire permet d’obtenir une efficacite dans 80 % des cas avec peu d’effets secondaires. C’est une excellente technique en cas d’echec de la corticotherapie ou en cas d’atteinte unilaterale.

Resume Objectif. – L’objectif de cette etude retrospective etait de juger l’interet d’une re-irradiation adjuvante chez des patientes atteintes d’un adenocarcinome mammaire de tres haut risque de seconde recidive locale. Patientes et Methodes. – Vingt patientes d’âge median 47 ans (29–65) ont ete traitees pour une neoplasie mammaire de facon conservatrice (tumorectomie, curage, puis radiotherapie externe du sein de 50 Gy en 25 fractions et 5 semaines voire des aires ganglionnaires, avec ou sans chimiotherapie et/ou hormonotherapie). Devant une recidive locale avec des facteurs de pronostic defavorable, elles ont eu une mastectomie et ont ete de janvier 1988 a septembre 2001 re-irradiees sur la paroi thoracique par des electrons ou des photons a une dose mediane de 45 Gy (33–65) delivree en 15 fractions et 33 jours. Les recidives locales etaient de type inflammatoires (4 patientes), multifocales (5 patientes), avec des nodules de permeation (5 patientes), retromammelonnaires (3 patientes) ou il y avait une atteinte des tranches de section avec infiltration musculaire ou cutanee (3 patientes). La duree mediane de surveillance etait de 48 mois (5–97). Resultats. – Quinze tumeurs n’ont pas recidive localement et parmi ces patientes, dix etaient vivantes et sans evolution a distance avec une duree mediane de surveillance de 52 mois (11–97). Il n’existait aucun lien significatif entre respectivement le taux de controle local et la dose biologique equivalente de re-irradiation ( p = 0,877) ou la surface de re-irradiation ( p = 0,424). Il a ete note cinq pneumopathies radiques sans insuffisance respiratoire, dont la survenue dependait de la dose biologique de re-irradiation ( p = 0,037) et des complications tardives a type de pigmentation marquee (12 patientes), de telangiectasies (8 patientes), de chondrite (2 patientes), de fibrose parietale (7 patientes), de fractures costales (4 patientes), de douleurs invalidantes (11 patientes) et de lymphœdemes (2 patientes). L’augmentation de la dose biologique equivalente etait liee de facon statistiquement tres significative a l’augmentation du risque d’apparition de douleurs invalidantes ( p = 0,0123). Conclusions. – La re-irradiation parietale permet d’obtenir un bon taux de controle local a long terme avec des taux de complications aigues acceptables, mais neanmoins des sequelles invalidantes, essentiellement douloureuses.

Experience accumulated over several decades with radiation of Head and Neck tumours by irradiation has demonstrated the need for a high tumour dose to achieve local control. With external beam irradiation alone, it is difficult to spare adjacent normal tissues, resulting in undesirable late effects on the salivary glands, mandible, and muscles of mastication. Interstitial implantation is ideally suited to deliver a high dose limited to the volume of the primary tumor, thus minimizing sequels. A large experience has been accumulated with low dose rate (LDR) brachytherapy in treatment of carcinoma of oral cavity, oropharynx, and nasopharynx. Recent analysis of large clinical series provided data indicating that modalities of low dose rate brachytherapy should be optimized in treating these tumors for increasing therapeutic ratio. Low dose rate brachytherapy is now challenged by high dose rate (HDR) brachytherapy and pulsed dose rate (PDR) brachytherapy. Preliminary results obtained with these two last modalities are discussed regarding to those of low dose rate brachytherapy.

Purpose/Objective(s) Breast cancer (BC) patients with comparable prognostic features have heterogeneous outcomes, partly because of radiotherapy resistance leading to loco-regional recurrences (LRR). The ProfiLER (Profilage LYric et Region, NCT01774409) clinical trial aims at establishing a simple genetic profile of metastatic cancers in order to offer patients personalized molecular targeted therapies. In the breast cancer area, the genomic profiling of a population who ultimately became metastatic, and its correlation with the patient outcome years after LRR, provided an opportunity to identify post hoc biomarkers of the initial radiation resistance. The aim of the present study was to determine if specific tumor genetic alterations were associated with radiation resistance, defined as a LRR despite optimal surgery, radiotherapy, and systemic adjuvant therapies, in a ProfiLER series. Materials/Methods Genetic profile of 162 BC patients’ tumors included in ProfiLER between 2013 and 2016 were analyzed using Next-Generation-Sequencing and Comparative-Genomic-Hybridization tests. Patients and tumor characteristics were analyzed for association with genomic rearrangements (mutations, amplification, homozygous deletions). Only gene alterations observed in >3% of the tumors, or included in well-known molecular pathways (PI3 Kinases pathway, MAP Kinases pathway, Tyrosine Kinase receptors family) were selected. The Cox multivariate analysis was based on (P3% of tumors. PIK3CA and ROS1 mutations were statistically correlated to the risk of LRR. A median loco-regional progression free survival (LRPFS) of 19.8 years was reported for PIK3CA mutation carriers (n = 34, 21%) versus 9.1 years for wild-type patients (HR = 0.29, 95% CI = 0.13-0.64, P = 0.002 in univariate analysis). PIK3CA mutation was identified as an independent protective factor of LRR using multivariate analysis (HR = 0.27, 95% CI = 0.09-0.82), P = 0.02). ROS1 mutated cancer patients (n = 8, 4.9%) had a median LRPFS of 4 years versus 16.1 years for wild-type patients (HR = 2.5, 95% CI = 1.74-7.05, P = 0.08 in univariate analysis), but was not identified as an independent LRR risk factor (HR = 2.45 95% CI = 0.83-7.26, P = 0.11 in multivariate analysis). Other mutations and amplifications were not associated with LRR. Among relapsing patients, the median time to LRR was nearly significantly different regarding status of the PIK3CA mutations, with 8.6 years for mutated patients versus4.7 years for non-mutated patients (P = 0.09). Conclusion PIK3CA mutation was associated with a lower risk of LRR in this BC population. ROS1 mutation was marginally associated with a higher risk of LRR, possibly because of a limited population. Results suggest PIK3CA and ROS1to be possible biomarkers of radio-sensitivity.

Malnutrition is frequent in head and neck (HN) and esophageal cancer patients and aggravated by radiochemotherapy (RCT), increasing morbi-mortality and treatment toxicity. Our goal was to investigate the effect of immunonutrition consisting of an arginine, omega-3 fatty acid, nucleotides-enriched diet on nutritional status, and functional capacity in HN or esophageal cancer patients undergoing RCT.37 patients were randomized in a double-blind clinical trial. 5 days before and until the end of RCT (5-7 weeks), they received either an Immunomodulating Enteral Nutrition (IEN) or an isonitrogenous, isoenergetic Standard Enteral Nutrition (SEN). Anthropometrical parameters, nutritional risk index (NRI), serum albumin, plasma antioxidant capacity, and functional capacity were recorded between the beginning and the end of RCT.A significant gain in total body weight (+2.1 ± 3.1 kg) was observed in IEN patients. Albuminemia and NRI were improved concomitantly in IEN malnourished patients. Plasma antioxidant capacity was improved (+100 ± 13 μM EqTrolox) in IEN patients. Functional capacity measured by WHO Performance Status and Karnofsky index was maintained in IEN patients but significantly reduced in SEN patients.These preliminary data show that immunonutrition could improve the nutritional status together with functional capacity in HN and esophageal cancer patients undergoing RCT.This clinical trial promoted by the University Hospital Center of Clermont-Ferrand has been registered at ClinicalTrial.gov website under the following reference: NCT00333099.

Head and neck cancers are the fifth among the most common cancers in France. Two thirds of cases occur at an advanced stage. For advanced disease, progression-free survival, despite undeniable progress, remains below 50% at three years. The last 20 years have been marked by the necessity to identify situations where less intense surgery and/or radiotherapy and/or chemotherapy is possible without jeopardizing the prognosis, and situations where a therapeutic intensification is necessary and results in a gain in survival while better preserving function with less toxicity. French cooperative groups gathering radiation oncologists (GORTEC), surgeons (GETTEC) and medical oncologists or physicians involved in the management of systemic treatments in head and neck cancers (GERCOR) are now belonging to the INCa-labelled Intergroup ORL to deal with the challenges of head and neck cancers.

Le but du traitement chirurgical du cancer epithelial de l’ovaire est de realiser une stadification anatomique precise et une reduction tumorale optimale.

Ductal carcinoma in situ is defined as breast cancer confined to the ducts of the breast without evidence of penetration of the basement membrane. Local treatment quality represents one of the most prognostic factors as half of recurrences are invasive diseases. The main goal of adjuvant radiotherapy after conservative surgery is to decrease local recurrences and to permit breast conservation with low treatment-induced sequelae. Several randomized trials have established the impact of 50 Gy to the whole breast in terms of local control. Nevertheless, no randomized trial is still available concerning the role of the boost in this disease. In this review, we present updated results of the literature and we detail the French multicentric randomized trial evaluating the impact of a 16 Gy boost after 50 Gy delivered to the whole breast in 25 fractions and 33 days. This protocol will start inclusions in October 2008.

To report preliminary results of a prospective study of intensity-modulated radiotherapy (IMRT) for head and neck squamous cell carcinoma (HNC) with bilateral irradiation of the neck.At the Alexis Vautrin Cancer Center, 23 patients have been treated with IMRT for HNC since January 2002-August 2003. The first 10 patients with a minimum follow-up of 3 months were analyzed. All tumors were oropharyngeal. There were four females and six males, with a mean age of 50 years (range 39-66). Stages were I-II in eight and III-IV in two. CTV1 was microscopic disease and N0 neck (prescribed dose : 50 Gy) and CTV2 was macroscopic disease and the volume at risk (prescribed dose: 66-70 Gy). PTV were CTV + 5 mm. Patient's immobilization consisted of a five-point head neck shoulder thermoplastic mask. Set-up verifications were done by semi-automatically matching portal images and digitized reconstructed radiographs. IMRT used dynamic multileaf collimation. Five patients (group A) received 50 Gy IMRT (two post-operative and three with a brachytherapy boost with a mean dose: 27.5 Gy), and five patients (group B) received 66-70 Gy IMRT (four post-operative). Acute and late normal tissue effects were graded according to the RTOG-EORTC radiation morbidity scoring criteria.With a median follow-up of 7.4 months (range 3-18.5), no patient died or had loco-regional relapse. The displacements were4 mm in 98% cases. CTV1 and 2 received 95% of the prescribed dose in 100% of the volume. On average the mean dose to the contralateral parotid was 25.5 Gy for group A vs. 31 Gy for group B (P = 0.09). Mean doses26 Gy were obtained in three of five patients in group A vs. zero of five patients in group B (P = 0.04). Acute skin toxicities were grade 1 in five patients, grade 2 in four and grade 3 in one. Acute mucositis cases were grade 1 in three patients, grade 2 in five and localized grade 3 in two. At 3 months, 50% of the patients had a grade 0-1 late xerostomia.The 26 Gy dose limit constraint to the contralateral parotid was easier to satisfy when IMRT was prescribed at a maximum dose of 50 Gy. Acute toxicity is low. The displacements in the mask indicate that it is possible to define the PTV as CTV + 4 mm. This reduction should decrease the mean dose to the parotids. At 3 months, a 50% rate of grade 0-1 late xerostomia encourages the hope of a very low rate at 2 years.

To retrospectively assess the efficacy of post-mastectomy re-irradiation for local relapse of breast cancer.Twenty patients, initially treated by conservative surgery and radiotherapy (50 Gy in 25 fractions over 5 weeks) were treated from 1998 to 2001 for a local relapse by salvage mastectomy and re-irradiation (either electron or photon beams). Mean age was 53 years (31-71). Reasons for re-irradiation were that the local relapses were inflammatory (4 pts), multifocal (5 pts), cutaneous (5 pts), involved the nipple (3 pts) or because the surgical margins (either muscle or skin) were involved (3 pts). The median dose of re-irradiation was 45 Gy (33-65) in 15 fractions over 33 days. Mean follow-up was 48 months (5-97).Fifteen patients remained free of a second local recurrence and 10 were still alive, without metastasis. Neither the dose of re-irradiation nor the irradiated surfaces were prognostic factors of local control (P = 0.877 and P = 0.424). Five patients developed radiation-induced pneumonitis without functional respiratory impairment. The incidence of pneumonitis seemed to be related to the biological dose of re-irradiation (P = 0.037). Other late complications occurred such as pigmentation changes (12 pts), telangiectasia (8 pts), chondritis (2 pts), parietal fibrosis (7 pts), rib fractures (4 pts), severe pain (11 pts) and lymphedema (2 pts). The increase in biological equivalent dose was highly statistically linked with the occurrence of disabling pain (P = 0.0123).Parietal re-irradiation achieves good and lasting local control with an acceptable rate of acute complications but with a risk of disabling late sequelae such as severe pain.

Experience accumulated over several decades with radiation of Head and Neck tumours by irradiation has demonstrated the need for a high tumour dose to achieve local control. With external beam irradiation alone, it is difficult to spare adjacent normal tissues, resulting in undesirable late effects on the salivary glands, mandible, and muscles of mastication. Interstitial implantation is ideally suited to deliver a high dose limited to the volume of the primary tumor, thus minimizing sequels. A large experience has been accumulated with low dose rate (LDR) brachytherapy in treatment of carcinoma of oral cavity, oropharynx, and nasopharynx. Recent analysis of large clinical series provided data indicating that modalities of low dose rate brachytherapy should be optimized in treating these tumors for increasing therapeutic ratio. Low dose rate brachytherapy is now challenged by high dose rate (HDR) brachytherapy and pulsed dose rate (PDR) brachytherapy. Preliminary results obtained with these two last modalities are discussed regarding to those of low dose rate brachytherapy.

e14730 Background: Pancreatic cancer remains resistant to many key cytotoxic chemotherapeutic agents and novel targeted therapies. The molecular heterogeneity of this cancer may account for therapy failures to date, although the growing arsenal of novel targeted agents could translate into patient survival. A better understanding of the cellular and molecular features of advanced disease will afford new opportunities for investigation, therapeutic intervention and clinical management of patients afflicted with pancreatic cancer. Methods: This study examined the expression profiles of Smad4 in 45 samples of surgically resected pancreatic cancer. Of these 45 patients, 32 underwent pancreaticoduodenectomy. The clinicopathological parameters, the histologic features were determined and correlated to the stage at initial diagnosis, patterns of failure (locally advanced v metastatic disease) and the status SMAD4 genes. Results: Among the 45 patients, 40% of patients died with metastatic disease and 15 % died with locally advanced evolution. SMAD4 genetic status was determined in 25 patients and seems to be correlated with a high grade histologic features and progression to metastasis. Complementary data about correlation between the mutational status of SMAD4 and survival will be presented during congress. Conclusions: SMAD4 gene inactivation seems to be associated with poorer prognosis and disease progression. Prospective validation of SMAD4 as a predictive biomarker may personalize treatment strategies for patients with pancreatic cancer.